1,407 research outputs found

    Deciphering the role of the sugar-induced transcription factor, Mondo in Drosophila Melanogaster

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    Overconsumption of sugar promotes the occurrence of metabolic disorders. Therefore, studying the mechanisms underlying our physiological responses to sugar helps identify the underlying molecular mechanisms and potential therapeutic targets. Mondo family transcription factors are evolutionarily conserved across a number of species including Drosophila melanogaster, and they are known as the key “sugar sensor” in our body. Lines of evidence indicate that this component is misregulated in insulin resistance and diabetes. The aims of my PhD thesis are to determine the function of fly Mondo and its interacting partner Mlx during different stages and in different nutrition states, and to globally identify its direct target genes and regulated pathways. A deficiency in Mondo and Mlx causes sugar inviability in flies fed on a high sugar diet. Furthermore, Mondo is essential for survival during starvation after sugar deprivation, which brings our attention to the involvement of Mondo in the regulation of nutrient usage and metabolic adaptation during starvation. The chromatin Mondo-Mlx binding profile reveals several known sugar-dependent Mondo target sites and potential new targets. The identified target genes are functionally clustered in metabolic pathways regarding sugar, lipid, and amino acids, which supports the concept that Mondo is a master metabolic regulator. Importantly, the data indicates that Mondo-Mlx is at the top of a regulatory network composed of abundant secondary transcriptional effectors. Motif searching analysis shows some interesting findings: in addition to the canonical ChoRE motif, a putative novel Mondo binding motif was also identified. Finally, our RNA Pol II ChIP-seq data provides the first direct evidence indicating that Mondo acts as both a transcriptional activator and repressor for different target genes and regulates gene transcription via influencing Pol II recruitment or elongation. Less is known about the role of Mondo family proteins in the nervous system, although Mondo expression has previously been observed in this metabolically active organ system. Here, I provide evidence of Mondo’s role in the central nervous system’s metabolism of sugar, lipids, and amino acids, specifically in the amino acids serine, glycine, and glutamine. Interestingly, the metabolism of lipid and serine in the fly brain has been shown to determine sleeping behaviors, though further investigation is necessary to test whether Mondo has a systemic role in controlling sleeping behaviors

    Macrophage-derived macrophage migration inhibitory factor mediates renal injury in anti-glomerular basement membrane glomerulonephritis

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    Macrophages are a rich source of macrophage migration inhibitory factor (MIF). It is well established that macrophages and MIF play a pathogenic role in anti-glomerular basement membrane crescentic glomerulonephritis (anti-GBM CGN). However, whether macrophages mediate anti-GBM CGN via MIF-dependent mechanism remains unexplored, which was investigated in this study by specifically deleting MIF from macrophages in MIFf/f−lysM−cre mice. We found that compared to anti-GBM CGN induced in MIFf/f control mice, conditional ablation of MIF in macrophages significantly suppressed anti-GBM CGN by inhibiting glomerular crescent formation and reducing serum creatinine and proteinuria while improving creatine clearance. Mechanistically, selective MIF depletion in macrophages largely inhibited renal macrophage and T cell recruitment, promoted the polarization of macrophage from M1 towards M2 via the CD74/NF-κB/p38MAPK-dependent mechanism. Unexpectedly, selective depletion of macrophage MIF also significantly promoted Treg while inhibiting Th1 and Th17 immune responses. In summary, MIF produced by macrophages plays a pathogenic role in anti-GBM CGN. Targeting macrophage-derived MIF may represent a novel and promising therapeutic approach for the treatment of immune-mediated kidney diseases

    catena-Poly[copper(II)-bis(μ-2,4-dichloro-6-formyl­phenolato)-κ3 O,O′:Cl 4;κ3 Cl 4:O,O′]

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    In the title compound, [Cu(C7H3Cl2O2)2]n, the CuII atom lies on a centre of inversion and adopts a [4+2] coordination mode, with two long axial Cu—Cl coordinative bonds complementing four Cu—O bonds from two 2,4-dichloro-6-formyl­phenolate ligands in a distorted square plane. π–π stacking inter­actions are also formed between neighbouring aromatic rings, with a centroid–centroid separation of 3.624 (2) Å

    3,5-Dibromo-2-hydroxy­benzaldehyde

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    The title compound, C7H4Br2O2, exhibits a layer packing structure via weak π–π stacking inter­actions [centroid–centroid distances between adjacent aromatic rings are 4.040 (8) and 3.776 (7) Å]. Mol­ecules in each layer are linked by inter­molecular O—H⋯O hydrogen bonding and Br⋯Br inter­actions [3.772 (4) Å]. There are two mol­ecules in the asymmetric unit

    Feature Fusion from Head to Tail for Long-Tailed Visual Recognition

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    The imbalanced distribution of long-tailed data presents a considerable challenge for deep learning models, as it causes them to prioritize the accurate classification of head classes but largely disregard tail classes. The biased decision boundary caused by inadequate semantic information in tail classes is one of the key factors contributing to their low recognition accuracy. To rectify this issue, we propose to augment tail classes by grafting the diverse semantic information from head classes, referred to as head-to-tail fusion (H2T). We replace a portion of feature maps from tail classes with those belonging to head classes. These fused features substantially enhance the diversity of tail classes. Both theoretical analysis and practical experimentation demonstrate that H2T can contribute to a more optimized solution for the decision boundary. We seamlessly integrate H2T in the classifier adjustment stage, making it a plug-and-play module. Its simplicity and ease of implementation allow for smooth integration with existing long-tailed recognition methods, facilitating a further performance boost. Extensive experiments on various long-tailed benchmarks demonstrate the effectiveness of the proposed H2T. The source code is available at https://github.com/Keke921/H2T.Comment: Accepted to AAAI24, similar to the conference version. Add the supplementr

    Antifungal effects of sisal leaf juice on Lasiodiplodia theobromae, the causal agent of mulberry root rot

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    This study was carried out to evaluate the antifungal activities of leaf juices (fresh juice, fermented juice, boiled juice and sterile juice) of nine sisal varieties on Lasiodiplodia theobromae, the causal agent of mulberry root rot. Results show that all the leaf juices could inhibit the mycelial growth in different degrees (the inhibitory rates ranged from 63.3 to 100%), due to different varieties and treatments. Among the nine varieties, the inhibition effects of hybrid 76416 and Agave americana were the best with absolute inhibition of all the leaf juice treatments against the mycelial growth, followed by Agave Amaniensis, Agave virdis, Agave angustifolia and Hybrid 11648. The inhibitory effect of some fresh juices would be cut down after being fermented, boiled and sterilized. The treated mycelia of L.theobromae were malformed, enlarged, broken and plasma leaked when observed under the microscope. Most of the leaf juices could inhibit the conidial germination absolutely, except A.amaniensis, H.11648 and A. angustifolia. The average germination rate of A. amaniensis, H.11648 and A. angustifolia was 72.4, 16.6 and 13%, respectively. The control efficiency of the fresh juice of H. 11648 against mulberry root rot in the field reached 73.1%.Key words: Sisal, leaf juice, anti-fungi, anti-fungal activities, mulberry root rot, Lasiodiplodia theobromae

    MUSCLE ACTIVATION AND THREE-DIMENSIONAL KINEMATICS OF UPPER EXTREMITY IN SNATCH WEIGHT LIFTING

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    INTRODUCTION: Previously, there was little weightlifting research focused on biomechanics of the elbow and the shoulder joints (Bartonietz, 1996). Therefore, the purposes of this study were to evaluate the kinematics of upper extremity on sagittal plane during 1st pull, transition from the 1st to the 2nd pull, 2nd pull, turnover under the barbell, catch phase, and rising from the squat position phases of snatch weight lifting and to examine upper-limb muscles activity during snatch weight lifting. The EMG signals were analyzed using the normalized linear envelopes

    Aberrant oligodendroglial-vascular interactions disrupt the blood-brain barrier, triggering CNS inflammation.

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    Disruption of the blood-brain barrier (BBB) is critical to initiation and perpetuation of disease in multiple sclerosis (MS). We report an interaction between oligodendroglia and vasculature in MS that distinguishes human white matter injury from normal rodent demyelinating injury. We find perivascular clustering of oligodendrocyte precursor cells (OPCs) in certain active MS lesions, representing an inability to properly detach from vessels following perivascular migration. Perivascular OPCs can themselves disrupt the BBB, interfering with astrocyte endfeet and endothelial tight junction integrity, resulting in altered vascular permeability and an associated CNS inflammation. Aberrant Wnt tone in OPCs mediates their dysfunctional vascular detachment and also leads to OPC secretion of Wif1, which interferes with Wnt ligand function on endothelial tight junction integrity. Evidence for this defective oligodendroglial-vascular interaction in MS suggests that aberrant OPC perivascular migration not only impairs their lesion recruitment but can also act as a disease perpetuator via disruption of the BBB

    3,5-Dichloro-2-hydroxy­benzaldehyde

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    The title compound, C7H4Cl2O2, exhibits a layer crystal structure; mol­ecules within each layer are linked by weak C—H⋯O inter­molecular hydrogen bonds. There is also an intramolecular O—H⋯O hydrogen bond

    Genetic testing of sperm donors in China: a survey of current practices

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    BackgroundThe National Health and Family Planning Commission of China (NHFPCC) issued the “Measures for the Management of Human Sperm Banks,” which was revised in 2003 and is still in effect today. One of the standard guidelines is that potential donors undergo laboratory testing to exclude infectious and genetic diseases and karyotype analysis. However, patient demands for donor genetic testing have also increased, and only karyotype analysis to exclude genetic diseases is not sufficient to meet these demands.ObjectiveTo examine donor genetic screening practices at sperm banks in China and to evaluate the qualifications and skills of genetic counselors at the banks.Materials and methodsAn electronic survey was distributed to twenty-seven sperm banks to examine donor genetic screening practices at sperm banks in China and to evaluate the qualifications and skills of genetic counselors at the banks. Twenty-six human sperm banks responded to a 32-question survey about their current practices related to genetic testing of sperm donors.ResultsThe 26 sperm banks reported that all qualified sperm donors undergo karyotype analysis; 22 banks (84.6%) collected three generations of family history from each qualified sperm donor; 10 (38.5%) reported that they attempted to accommodate special requests from donor semen recipients for particular genetic tests. Only 2 of the 26 (7.7%) sperm banks reported that they performed whole-exome sequencing. At all the sperm banks, consent for genetic testing was obtained as part of the overall contract for sperm donors. Nineteen (73.1%) sperm banks had genetic counselors on their staff, while six (23.1%) had no genetic counselors on their staff but had access to genetic counselors at the hospital. Only one (3.8%) sperm bank had no genetic counselors on their staff or at the hospital.ConclusionsThe need for larger scale genetic testing of donors and recipients and an extensive panel of genetic tests specific to the Chinese population. Additionally, professionally trained geneticists must be employed as genetic counsellors so that the results of genetic tests and their implications can be explained to donors
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